Anticonvulsant Effects of Lippia citriodora (Verbenaceae) Leaves Ethanolic Extract in Mice: Role of GABAergic System

Background: Lippia citriodora Kunth is one of the Iranian traditional medicines for the treatment of convulsive disorders. The goal of this study is to investigate the anticonvulsant activity of the plant’s leave ethanolic extract against electro‑ and chemoconvulsant‑induced seizures in mice. Methods: The anticonvulsant activity of the extract (200, 400, 800 mg/kg, per os, p.o.) was investigated in pentylenetetrazole (PTZ) and maximal electroshock (MES)‑induced seizures in mice. Diazepam (1 mg/kg) and phenytoin (25 mg/kg) intraperitoneally (i.p.) were used as reference drugs. In addition, for investigating the role of GABAergic system, flumazenil (2 mg/kg, i.p.) was also injected before L. citriodora. Results: The extract had not any toxicity and significantly decreased the duration and increased the latency of the seizures induced by PTZ (90 mg/kg). In the MES test, L. citriodora displayed statistically significant reduction in hind limb tonic extension duration in a nondose‑dependent manner. Flumazenil reversed the anticonvulsant activity of the plant’s extract in the PTZ model. Conclusions: The results propose that L. citriodora leave ethanolic extract has anticonvulsant activity against convulsive disorders. It seems that this plant’s extract generates its antiseizure effect through GABAergic system potentiation. Further studies will be needed in order to investigate the exact mechanisms of it. Moreover, one may conclude that the present results are in accordance with the positive effect of L. citriodora extract to treat convulsion mentioned in old Iranian literature.